Glucocorticoids are important for the maintenance of homeostasis. The release of glucocorticoids is regulated by the hypothalamic-pituitary-adrenal (HPA) axis. The lateral septum is involved in the control of a variety of physiological and behavioral processes such as memory and learning, emotions, fear, aggression, and the stress response. The lateral septum is a possible area of stress regulation prior to its interactions with the HPA axis. Emerging evidence strongly implicates the lateral septum as a prominent subcortical relay of stress-related hippocampal output. The lateral septum receives glutamaterigc signals from the hippocampus, which is believed to inhibit the HPA axis. Recent data indicate that the lateral septum is preferentially activated by psychological stressors and differentially modulated by prolonged stress exposure, suggesting a role in stress integration. I hypothesize that the lateral septum is involved in inhibition of HPA responses to psychological stress. The goals of this proposal are 1) to determine which hypothalamic PVN-projecting regions receive lateral septal terminals, 2) to determine the neurochemical phenotype of PVN-projecting neurons that receive lateral septal terminal, and 3) to determine the role of glutamate activation of lateral septal neurons in HPA axis regulation.